The ability to lower the temperature of organs, tissues or a whole organism without causing extensive damage is of the highest interest for both preservation and transplantation applications as well as for the development of hypothermic surgery. In the first case, lowering the temperature as much as possible is important to extend the storage time between organ harvesting and transplantation. But so far, the lack of adequate cryoprotection systems for tissues and organs has prevented lowering the temperature of organs to below freezing temperatures during organ transportation and storage. Such temperatures damage the tissue, especially the fragile vasculature of the organs such as the lungs, the liver or the heart. (http://www.britannica article: “Transplant”, sub-section: “organ and tissue banks”).
The damage done to the cells and vasculature of tissues upon freezing is the result of two deleterious processes: osmotic stress caused by an increase in solute concentration when ice crystals form, and the physical damage (i.e. cellular rupture and vascular puncturing) caused by ice crystal growth. (Belzer F. O., Southard J. H., Principles of solid-organ preservation by cold storage. Transplantation. 1988, 45, 673-676)
In the same way, the development of hypothermic surgery for operations of the heart or the brain has been hindered by the lack of adequate cryoprotective blood replacement liquid that would allow a surgeon to intervene for a longer time on a body in a state of blood flow interruption and reduced metabolism.
A greater degree of cryoprotection of tissue vasculature has been accomplished through blood substitutes containing various solutes. For example, small molecules such as glycerol and DMSO have been employed. These solutes beneficially penetrate cells and provide intra- and extracellular protection, but their concentrations are limited due to toxicity. Polymers such as substituted starches, dextran, and polyethylene glycol have also been employed. See, e.g., U.S. Pat. Nos. 5,405,742 and 4,938,961. These materials do not penetrate the cell, but can beneficially decrease the freezing point of the physiological liquids and additionally may limit crystal formation and growth in the vasculature. However, the polymer concentrations necessary to substantially reduce crystal growth tend to possess an unacceptably high viscosity (which makes it very difficult to pump into small vasculature). Antifreeze proteins from organisms, which live in sub-freezing temperatures, have also been explored as cryoprotective solutions. Particles of poly(2-hydroxyethyl methacrylate) have been used for endovascular embolization, but use for cryoprotection was not disclosed (Horak, et al., Biomaterials, 1986, 7:188-190).
A low-toxicity solution that optimally protects vasculature and organs against ice crystal growth and osmotic stress has yet to be achieved.